The over-all purpose is to elucidate interactions between lead and renal function in terms of three questions: What are the mechanisms and determinants of renal lead excretion? What is the effect of chronic lead-poisoning on renal sodium handling, and the renin-angiotensin system? What is the effect of chronic lead-poisoning on plasma concentration of erythropoietin? Experiments will be performed on normal and chronically lead-poisoned dogs and rats, using renal clearance techniques and stop-flow analysis. We will determine how much plasma lead is ultrafilterable and what combination of glomerular filtration, tubular reabsorption, and secretion account for lead excretion. We will determine whether the pattern changes with the degree and duration of lead-poisoning, and how it is changed by alterations of dietary calcium, parathormone, thyrocalcitonin, and vitamin D. The effect of lead on tubular sodium reabsorption during low-sodium and normal diets and during a saline load will be measured. The responses of renin secretion, various components of the renin- angiotensin-aldosterone system, and plasma erythropoietin to a variety of stresses (sodium depletion, hypotension, hypoxia) will be evaluated in chronically lead-poisoned animals. We hope to establish the minimal dose-time required for the appearance of observable changes in these parameters.